Is TRIM59 p.Pro11Ser (c.31C>T) pathogenic?

TRIM59 p.Pro11Ser (c.31C>T) is classified Uncertain significance in TRIM59 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-12). AlphaMissense: likely benign (0.185); No allele count reported in gnomAD v4.1 (AN 1,503,930).

How common is TRIM59 p.Pro11Ser (c.31C>T) in the general population?

TRIM59 p.Pro11Ser (c.31C>T) is no allele count reported in gnomAD v4.1 (AN 1,503,930) (gnomAD).

What do computational predictors say about TRIM59 p.Pro11Ser (c.31C>T)?

AlphaMissense predicts likely benign (score 0.185) — an in-silico prediction, not a clinical call.

TRIM59 p.Pro11Ser

c.31C>T · VCV3461499

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.185 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,503,930)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.185	likely benign
REVEL	0.307	indeterminate
SaProt	LLR -6.21	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.1	GERP 1.9, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 1,208 bp · p 0.72 · regional, not allelic
Overall
CADD	15.31	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,503,930). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: TRIM59
Protein: p.Pro11Ser
Coding: c.31C>T
MANE Select: NM_173084
Type: single nucleotide variant
Location: chr3:160439153 (GRCh38)
Gene constraint: LOEUF 0.675 · pLI 0.12 (gnomAD)
Structure: AlphaFold pLDDT 84.52

Full TRIM59 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TRIM59 p.Arg21His Uncertain significance ★ ⚠ same type
TRIM59 p.Arg60Gly Uncertain significance ★ ⚠ same type
TRIM59 p.Asn215Tyr Uncertain significance ★ ⚠ same type
TRIM59 p.Asn377Ser Uncertain significance ★ ⚠ same type
TRIM59 p.Asn384Ser Uncertain significance ★ ⚠ same type
TRIM59 p.Asp181Tyr Uncertain significance ★ ⚠ same type
TRIM59 p.Asp209Gly Uncertain significance ★ ⚠ same type
TRIM59 p.Cys109Arg Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/trim59-p-pro11ser (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown